Synthesis-Stuttgart最新文献

Synthetic Studies toward Anguidine: Assembly of the Tricyclic Ether Scaffold. 胍的合成研究：三环醚支架的组装。

IF 2.2 4区化学

Synthesis-Stuttgart Pub Date : 2026-10-07 DOI: 10.1055/a-2965-4545

Yingzhao Zhao, Frank R Fronczek, Prakash T Parvatkar, Roman Manetsch

{"title":"Synthetic Studies toward Anguidine: Assembly of the Tricyclic Ether Scaffold.","authors":"Yingzhao Zhao, Frank R Fronczek, Prakash T Parvatkar, Roman Manetsch","doi":"10.1055/a-2965-4545","DOIUrl":"10.1055/a-2965-4545","url":null,"abstract":"Anguidine, a type A trichothecene (TCN) isolated from Fusarium graminearum, features a highly functionalized 6/6/5 tricyclic scaffold incorporating a central six-membered ether ring and a C12-C13 epoxide. Its pronounced bioactivity and structural complexity render it a challenging synthetic target. Herein, we describe our synthetic investigations toward anguidine and its tricyclic ether scaffold. An initial model study enabled efficient construction of the 6/5/6 tricyclic framework through a sequence comprising intramolecular aldol condensation, 1,2-addition, and acid-catalyzed intramolecular cyclization as the key transformations. This strategy established the fused carbocyclic system featuring a central ether linkage in a concise, convergent manner. Application of this approach to the total synthesis of anguidine commenced with the assembly of a highly functionalized cyclopentane precursor, featuring key transformations such as Wittig olefination and dihydroxylation. Subsequent 1,4-conjugate addition, intramolecular aldol condensation, 1,2-addition, and intramolecular cyclization were designed to construct the tricyclic framework that encompasses the full carbon skeleton of anguidine. Although advanced intermediates bearing the required connectivity were successfully obtained, completion of the total synthesis proved challenging due to the steric hindrance associated with the pre-functionalized cyclopentane precursor.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Biological Evaluation of O6C-Salvinorin Alkyne Probes. O6C-Salvinorin炔探针的合成及生物学评价

IF 2.2 4区化学

Synthesis-Stuttgart Pub Date : 2026-09-15 DOI: 10.1055/a-2945-3974

Etienne Cotter, Giovanni Leoni, Nathan Dao, Sarah J Hill, Alexandra Faragher, Vuong Q Dang, Laura M Bohn, Ryan A Shenvi

{"title":"Synthesis and Biological Evaluation of O6C-Salvinorin Alkyne Probes.","authors":"Etienne Cotter, Giovanni Leoni, Nathan Dao, Sarah J Hill, Alexandra Faragher, Vuong Q Dang, Laura M Bohn, Ryan A Shenvi","doi":"10.1055/a-2945-3974","DOIUrl":"10.1055/a-2945-3974","url":null,"abstract":"The salvinorins represent a unique class of polyoxygenated, non-nitrogenous diterpenes that potently and selectively modulate the kappa-opioid receptor (KOR). We recently disclosed a de novo asymmetric synthesis of this scaffold that enabled the discovery of highly potent, biased analogs, including C11-alkynes designed for the CATCH (Clearing-Assisted Tissue Click Chemistry) assay. Here, we report an optimized, scalable synthetic route that substitutes a problematic 1,4-conjugate addition of a Grignard reagent with a robust organozinc protocol in DMA, and improves a samarium-mediated Reformatsky reaction via the addition of LiBr. These methodological improvements facilitated the scalable synthesis of two highly active positive-control probes and three tailored negative-control probes, including functionally silent and cross-linking deficient analogs. A screen of >300 GPCRs confirmed the exceptional KOR selectivity of the novel alkyne probe, establishing it as a promising tool poised to validate target-specific engagement in situ, an application currently under investigation.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homo-Clavulyne: Evaluation of a One-Atom Ring Expansion Strategy to Stabilize the Nine-Membered Ring Enediyne Biosynthetic Precursor. 同型克拉维炔：稳定九元环内二炔生物合成前体的单原子扩环策略的评价。

IF 2.2 4区化学

Synthesis-Stuttgart Pub Date : 2026-09-14 DOI: 10.1055/a-2951-5568

Lande Hu, Myungeun Jeong, Mohammad R Seyedsayamdost, Erik J Sorensen

引用次数: 0

A Stereoconvergent Annulation in the Synthesis of Lysergic Acid. 麦角酸合成中的立体会聚环。

IF 2.2 4区化学

Synthesis-Stuttgart Pub Date : 2026-08-31 DOI: 10.1055/a-2939-5845

Zackary D Firestone, Ryan C Harbit, Joel M Smith

引用次数: 0

Late-stage Diversification of HIV-1 Protease Inhibitor via SuFEx Click Chemistry. 通过SuFEx点击化学实现HIV-1蛋白酶抑制剂的后期多样化。